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| General |
| Study Status |
Completed |
Application Number /
Requirement Number |
P180001 / PAS001 |
| Date Original Protocol Accepted |
12/31/2018
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| Date Current Protocol Accepted |
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| Study Name |
Continued f/u of pivotal study
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| Device Name |
Zenith Dissection Endovascular System
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| Clinical Trial Number(s) |
NCT01568320 NCT02094300 NCT02464943
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| General Study Protocol Parameters |
| Study Design |
Prospective Cohort Study
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| Data Source |
New Data Collection
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| Comparison Group |
No Control
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| Analysis Type |
Descriptive
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| Study Population |
Transit.Adolescent B(as adults): 18 yrs < 22 yrs,
Adult: At least 22 yrs
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| Detailed Study Protocol Parameters |
| Study Objectives |
The objective of this study is to obtain long-term follow-up and additional information regarding the treatment of all types of dissections and reasons for repair.
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| Study Population |
Patients with acute or chronic dissections.
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| Sample Size |
Follow-up data on the surviving patients of the 73 enrolled in the IDE pivotal study will be reported in the Continued Follow-up of the Zenith Dissection Endovascular System Pivotal Study. 120 new patients with acute Type B dissections, who are treated using both the Zenith TX2 Dissection Endovascular Graft with Pro-Form and the Zenith Dissection Endovascular Stent, and 60 new patients with chronic Type B dissections, who are treated using the Zenith Dissection Endovasular System, will be included in the Zenith Dissection Endovascular System Post Approval Study.
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| Key Study Endpoints |
The following endpoints will be reported through 5-years for the Continued Follow-up of the Zenith Dissection Endovascular System Pivotal Study: false lumen characteristics (i.e., diameter change, patency, and source of persistent flow), dissection-related deaths, aortic ruptures, aortic enlargements, extension of the dissection, major adverse events (i.e., paraparesis, paraplegia, new ischemia), losses of device integrity, and additional dissection-related interventions, including the reasons for the interventions.
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| Follow-up Visits and Length of Follow-up |
5 years
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| Interim or Final Data Summary |
| Actual Number of Patients Enrolled |
Seventy-three (73) subject including 67 from the US and 6 from Japan
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| Actual Number of Sites Enrolled |
Twenty-two (22) sites including 21 sites in the US at 1 site in Japan
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| Patient Follow-up Rate |
Clinical follow-up was 86.1% (31/36) at 5 years; CT Scan was completed in 86.1% (31/36) of subjects at 5 years.
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| Final Safety Findings |
The 30-day freedom from major adverse events (MAE) rate was 71.6% for the pivotal study compared to performance goal (PG) of 51.2% (p < 0.001). The 30-day survival rate was 95.5% compared to the PG of 79.4% (p < 0.001). Therefore, the pivotal study met both primary safety and effectiveness endpoints for the Zenith Dissection Endovascular System.
Secondary Endpoints
Serious Adverse Events (SAEs) at 5-year timepoint for all patients were: all-cause mortality 7.3% (3/41), Dissection related mortality 0% (0/41), Aortic Rupture 2.4% (1/41) and Conversion 0% (0/41).
Major Adverse Events (MAEs): defined as myocardial infarction, Renal failure, Bowel ischemia, Stroke, paraplegia, paraparesis, prolong ventilatory support. A total of 26 patients experienced MAEs
The rate at 5-year timepoint for each of the MAEs was 0% (0/41).
Secondary intervention: Overall, 22 patients received secondary interventions through 5 years which includes ancillary component placement, balloon angioplasty, coil embolization, thrombectomy, percutaneous stent placement, conversion to open repair and surgical bypass procedure.
True and False lumen diameters at location of maximum aortic diameter:
(a) Within the stent-graft - mean true lumen diameter increased (> 5 mm) whereas the mean false lumen diameter decreased (> 5 mm) from post-procedure through 5-year in all patients and in the subgroups with and without a Dissection Stent.
(b) Within the Dissection Stent region- mean true lumen diameter increased (> 5 mm) whereas the average false lumen diameter remained stable (less than or equal to 5 mm change) from post-procedure through 5-year follow-up.
(c) Distal to treated Segment - mean true lumen diameter appeared stable from post-procedure through 5-year follow-up (= 5 mm change), whereas the average false lumen diameter appeared to increase (> 5 mm) through 5-year follow-up for all patients and the subgroups
Change in transaortic diameter (true lumen + false lumen diameter) in the stent graft region compared to first post procedure exam:
The percentage of all patients that experienced an increase in transaortic growth within the stent graft region at 2, 3, 4 and 5 years was 23.8% (10/42), 22.5% (9/40), 27.8% (10/36) and 17.2% (5/29) respectively.
The percentage of patients that experienced a decrease in transaortic growth within the stent graft region at 2, 3, 4 and 5 years was 19.0% (8/42), 17.5% (7/40), 19.4% (7/36) and 20.7% (6/29) respectively.
The percentage of patients with no change in transaortic growth within the stent graft at 2, 3, 4 and 5 years was 57.1% (24/42), 60.0% (24/40), 52.8% (19/36) and 62.1% (18/29), respectively.
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| Final Effect Findings |
(continued)
Entry Flow in the Thoracic Aorta
The percentage of all patients with Type I (proximal) entry flow into thoracic false lumen at 2, 3, 4 and 5 years was 12.2% (5/41), 5.1% (2/39), 2.9% (1/35) and 0% (0/28), respectively.
The percentage of all patients with Type I (distal) entry flow into thoracic false lumen from 2 through 5 years was zero (0%) at each time point. There were no reports (0%) of Type II, III or IV entry flow.
The percentage of all patients with entry flow into thoracic false lumen via collateral at 2, 3, 4 and 5 years was 36.6% (15/41), 35.9% (14/39), 20.0% (7/35) and 17.9% (5/28) respectively.
The percentage of all patients with entry flow into thoracic false lumen via secondary tear at 2, 3, 4 and 5 years was 14.6% (6/41), 25.6% (10/39), 20.0% (7/35) and 17.9% (5/28), respectively.
Entry Flow in the Abdominal Aorta
There were no reports (0%) of Type I, II, III or IV entry flow into the abdominal false lumen from 2 through 5 years in all patients.
The percentage of all patients with entry flow into abdominal false lumen via collateral at 2, 3, 4 and 5 years was 64.9% (24/37), 70.3% (26/37), 68.6% (24/35) and 65.5% (19/29) respectively.
The percentage of all patients with entry flow into abdominal false lumen via secondary tear at 2, 3, 4 and 5 years was 56.8% (21/37), 70.3% (26/37), 68.6% (24/35) and 58.6% (17/29), respectively.
False lumen Status
At 2, 3, 4 and 5 years the false lumen was completely thrombosed within the stent graft for 62.5% (25/40), 63.2% (24/38), 76.5% (26/34) and 75.0% (21/28) respectively for all patients.
At 2, 3, 4 and 5 years, the false lumen was partially thrombosed within the dissection stent for
73.3% (22/30), 70.0% (21/30), 84.6% (22/26) and 61.9% (13/21), respectively for all patients who received dissection stent.
At 2, 3, 4 and 5 years there were no apparent false lumen proximal to the treated region for 100% (41/41), 97.4% (38/39), 97.1% (33/34) and 100% (28/28), respectively of all patients.
At 2, 3, 4 and 5 years, false lumen distal to the treated segment was partially thrombosed for
52.8% (19/36), 55.3% (21/38), 48.5% (16/33) and 50.0% (13/26) of all patients.
Progression of Dissection:
A total of seven (7) patients were reported to have had retrograde/proximal extension of dissection and two patients (2) had antegrade/distal extension of dissection.
Device Integrity
There were no reports of device integrity issues (0%) for all patients from 2 through 5 years.
Device Migration
Device migration was reported in 7.7% (3/39), 7.5% (3/40), 0% (0/35) and 0% (0/29) of all patients at 2, 3, 4 and 5 years respectively.
Device Component Separation occurred in 2.4% (1/42), 4.8% (2/42), 2.9% (1/35) and 6.9% (2/29) of all patients at 2, 3, 4 and 5 years, respectively.
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| Study Strengths & Weaknesses |
Study Strength: Majority of the study patients (91.7%, 67/73) were enrolled at sites in the United States. The primary safety endpoint for the Zenith Dissection Endovascular System was met in the pivotal study with 30-day MAE rate of 71.6% compared to PG of 51.2% (p <0.001) in support of safety of this device. Primary effectiveness of 30-day survival was also met with survival rate of 95.5% compared to PG of 79.4% (p< 0.0001). Clinical follow-up and CT scan evaluation were achieved for 86% all patients at 5 years for each assessment.
Weakness: the long-term results are descriptive analyses only.
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| Recommendations for Labeling Changes |
Labeling change is recommended to reflect the long-term results of the Continued Follow-up Study.
The labeling change should include a new section on the label showing a summary of the study results (final endpoint results, follow-up rate etc.), strengths and limitations of long-term Study.
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